{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T11:04:55Z","timestamp":1770894295815,"version":"3.50.1"},"reference-count":83,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T00:00:00Z","timestamp":1655078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science, Technology and Innovation Funding Authority, STIFA","award":["project#33494"],"award-info":[{"award-number":["project#33494"]}]},{"name":"Science, Technology and Innovation Funding Authority, STIFA","award":["R34"],"award-info":[{"award-number":["R34"]}]},{"DOI":"10.13039\/501100009229","name":"American University in Cairo","doi-asserted-by":"publisher","award":["project#33494"],"award-info":[{"award-number":["project#33494"]}],"id":[{"id":"10.13039\/501100009229","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009229","name":"American University in Cairo","doi-asserted-by":"publisher","award":["R34"],"award-info":[{"award-number":["R34"]}],"id":[{"id":"10.13039\/501100009229","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Ectodermal dysplasia (ED) are hereditary disorders characterized by the disturbance of the ectodermal development of at least two of four ectodermal tissues: teeth, hair, nails and sweat glands. Clinical classification of ED is challenged by overlapping features, variable expressivity, and low number of patients, hindering full phenotypic spectrum identification. Disease-causing variants in elements of major developmental pathways, e.g., Ectodysplasin\/NF\u03baB, Wnt, and Tp63 pathways, have been identified in fewer than half of ED phenotypes. Whole-exome sequencing (WES) was performed for ten Egyptian ED patients presenting with tooth agenesis, normal sweating, scalp hypotrichosis, and sharing characteristic facial features. WES was followed by in silico analysis of the effects of novel detected genetic variants on mRNA and protein structure. The study identified four novel rare pathogenic and likely pathogenic TSPEAR variants, a gene which was recently found to be involved in ectodermal organogenesis. A novel in-frame deletion recurred in eight patients from six unrelated families. Comparing our cohort to previously reported TSPEAR cohorts highlighted the influence of ethnicity on TSPEAR phenotypic affection. Our study expands the clinical and mutational spectrum of the growing TSPEAR associated phenotypes, and pinpoints the influence of WES and in silico tools on identification of rare disease-causing variants.<\/jats:p>","DOI":"10.3390\/genes13061056","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T22:00:38Z","timestamp":1655157638000},"page":"1056","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Confirmation of a Phenotypic Entity for TSPEAR Variants in Egyptian Ectodermal Dysplasia Patients and Role of Ethnicity"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1913-4650","authenticated-orcid":false,"given":"Eman A.","family":"Rabie","sequence":"first","affiliation":[{"name":"Medical Molecular Genetics Department, Human Genetics & Genome Research Division (HGGR), National Research Centre (NRC), Cairo 12622, Egypt"},{"name":"Biology Department, School of Sciences and Engineering, The American University in Cairo (AUC), Cairo 11835, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inas S. M.","family":"Sayed","sequence":"additional","affiliation":[{"name":"Orodental Genetics Department, Human Genetics & Genome Research Division (HGGR), National Research Centre (NRC), Cairo 12622, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khalda","family":"Amr","sequence":"additional","affiliation":[{"name":"Medical Molecular Genetics Department, Human Genetics & Genome Research Division (HGGR), National Research Centre (NRC), Cairo 12622, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hoda A.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Medical Molecular Genetics Department, Human Genetics & Genome Research Division (HGGR), National Research Centre (NRC), Cairo 12622, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mostafa I.","family":"Mostafa","sequence":"additional","affiliation":[{"name":"Orodental Genetics Department, Human Genetics & Genome Research Division (HGGR), National Research Centre (NRC), Cairo 12622, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8902-9018","authenticated-orcid":false,"given":"Nehal F.","family":"Hassib","sequence":"additional","affiliation":[{"name":"Orodental Genetics Department, Human Genetics & Genome Research Division (HGGR), National Research Centre (NRC), Cairo 12622, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heba","family":"El-Sayed","sequence":"additional","affiliation":[{"name":"Clinical Genetics Department, Human Genetics & Genome Research Division (HGGR), National Research Centre (NRC), Cairo 12622, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suher K.","family":"Zada","sequence":"additional","affiliation":[{"name":"Biology Department, School of Sciences and Engineering, The American University in Cairo (AUC), Cairo 11835, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghada","family":"El-Kamah","sequence":"additional","affiliation":[{"name":"Clinical Genetics Department, Human Genetics & Genome Research Division (HGGR), National Research Centre (NRC), Cairo 12622, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1002\/ajmg.a.61045","article-title":"Ectodermal dysplasias: Classification and organization by phenotype, genotype and molecular pathway","volume":"179","author":"Wright","year":"2019","journal-title":"Am. 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